Abstract
The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or ‘disconnectivity’) arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays, few imaging studies have specifically examined its maturation throughout early infancy and childhood. Thus, direct investigations of the relationship(s) between evolving behavioral and cognitive functions and the myelination of the supporting neural systems have been sparse. Further, without knowledge of the ‘normative’ developmental time-course, identification of early abnormalities associated with developmental disorders remains challenging. In this work, we examined the use of longitudinal (T1) and transverse (T2) relaxation time mapping, and myelin water fraction (MWF) imaging to investigate white matter and myelin development in 153 healthy male and female children, 3 months through 60 months in age. Optimized age-specific acquisition protocols were developed using the DESPOT and mcDESPOT imaging techniques; and mean T1, T2 and MWF trajectories were determined for frontal, temporal, occipital, parietal and cerebellar white matter, and genu, body and splenium of the corpus callosum. MWF results provided a spatio-temporal pattern in-line with prior histological studies of myelination. Comparison of T1, T2 and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information.
Highlights
Many psychiatric disorders are being considered within the context of a neurodevelopmental disorder
Our results show that 1) albeit challenging, high quality MR imaging can be successfully and routinely performed within non-sedated infants, toddlers and 60 months 15 5 20 1716/2040 1778 young children; 2) derived spatio-temporal of myelin water fraction (MWF) changes is in good agreement with histological studies of myelin maturation; and 3) care should be taken in linking relaxation time changes with myelin changes
To acquire whole-brain, higher spatial resolution (1.8 × 1.8 × 1.8 mm3 voxel dimensions) MWF maps, we utilized a rapid alternative to multiecho spin-echo (MESE), termed mcDESPOT, which derives the MWF from spoiled gradient echo (SPGR, spoiled FLASH) and fully-balanced steady-state free precession data acquired over a range of flip angles
Summary
Many psychiatric disorders are being considered within the context of a neurodevelopmental disorder These include disorders such as autism, attention deficit disorder and schizophrenia (Courchesne et al, 2011; Grossman et al, 2003; Wolff et al, 2012), which potentially arise from atypical brain development over the first few years of life. Evidence for a close relationship between cognitive maturation and the myelination of underlying neural systems comes principally from indirect association studies combining post-mortem studies of myelination and neurobehavioral studies on healthy infants (Melina, 2004; Rabinowics, 1986). Magnetic resonance imaging (MRI) affords a more direct means of examining these relationships in the same infants by, for example, associating changes in MRI metrics (e.g. white or gray matter ‘density’, cortical thickness, diffusion anisotropy, or relaxation time) with measures of functional or behavioral
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